Methods of improving bone-soft tissue healing using electrospun fibers

ABSTRACT

The instant disclosure is directed to methods of improving bone-soft tissue healing using biocompatible electrospun polymer fibers. In one embodiment, a method may include locating a portion of a subject&#39;s bone, affixing a tendon or ligament to the bone using a hardware fixture, and placing a patch comprising at least one electrospun polymer fiber in physical communication with both the bone and the tendon or ligament. In some embodiments, the bone may be a humerus, and the tendon or ligament may be a supraspinatus tendon. In certain embodiments, the patch may comprise substantially parallel electrospun polymer fibers, and may be placed such that the fibers are also substantially parallel with the long axis of the tendon or ligament.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to and benefit of U.S. ProvisionalApplication Ser. No. 62/453,737, filed Feb. 2, 2017, entitled “Methodsof Improving Bone-Soft Tissue Healing Using Electrospun Fibers,” U.S.Provisional Application Ser. No. 62/583,530, filed Nov. 9, 2017,entitled “Methods of Improving Bone-Soft Tissue Healing UsingElectrospun Fibers,” and U.S. Provisional Application Ser. No.62/596,179, filed Dec. 8, 2017, entitled “Methods of Improving Bone-SoftTissue Healing Using Electrospun Fibers,” each of which is herebyincorporated herein by reference in its entirety.

BACKGROUND

When soft tissue, such as a tendon or ligament, tears or ruptures andpulls away from the bone to which it is attached, surgery is necessary.In a typical reconstruction surgery, such as a rotator cuff or Achillestendon repair, a suture and suture anchor are typically used to securethe soft tissue back to the bone. Once it is “reattached” to the bone,the soft tissue and bone are expected to heal to reform a strongbone-soft tissue interface. Frequently, however, such healing issuboptimal, or is at risk for re-rupture during the healing period.Therefore, a need exists to decrease the healing time and improve thequality of the repair of the soft tissue to the bone to more closelyapproximate the strength and quality seen at an uninjured bone-softtissue interface.

SUMMARY

The instant disclosure is directed to methods of improving bone-softtissue healing using biocompatible electrospun polymer fibers. In oneembodiment, a method may include locating a portion of a subject's bone,affixing a tendon or ligament to the bone using a hardware fixture, andplacing a patch comprising at least one electrospun polymer fiber inphysical communication with both the bone and the tendon or ligament. Insome embodiments, the bone may be a humerus, and the tendon or ligamentmay be a supraspinatus tendon. In certain embodiments, the patch maycomprise substantially parallel electrospun polymer fibers, and may beplaced such that the fibers are also substantially parallel with thelong axis of the tendon or ligament. In other embodiments, the patch maycomprise randomly oriented electrospun polymer fibers.

In another embodiment, a method may comprise locating a humerus of asubject, affixing a supraspinatus tendon to the humerus using a hardwarefixture, and placing a patch comprising at least one electrospun polymerfiber in physical communication with the humerus and the supraspinatustendon, such that the patch is between the humerus and the supraspinatustendon, and the suture extends through an opening in the patch. Furtherembodiments of the instant disclosure are described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates with a suture in communication with a suture anchorextending through a patch, in accordance with the instant disclosure.

FIG. 2 illustrates an alternative view of a suture in communication witha suture anchor extending through a patch, in accordance with theinstant disclosure.

FIG. 3A illustrates a histological sample of a native ovine rotatorcuff.

FIG. 3B illustrates a histological sample of an ovine rotator cuff, at 6weeks, repaired without using a scaffold in accordance with the instantdisclosure.

FIG. 3C illustrates a histological sample of an ovine rotator cuff, at 6weeks, repaired with a scaffold in accordance with the instantdisclosure.

FIG. 4A illustrates a histological sample of a native ovine rotatorcuff.

FIG. 4B illustrates a histological sample of an ovine rotator cuff, at12 weeks, repaired without using a scaffold in accordance with theinstant disclosure.

FIG. 4C illustrates a histological sample of an ovine rotator cuff, at12 weeks, repaired with a scaffold in accordance with the instantdisclosure.

FIG. 5 illustrates ultimate failure load data (N) in 6-week and 12-weeksamples for each of three experimental groups in an ovine model ofrotator cuff repair, in accordance with the instant disclosure. Adenotes p=0.003; B denotes p=0.007.

FIG. 6 illustrates construct stiffness data (N/mm) in 6-week and 12-weeksamples for each of three experimental groups in an ovine model ofrotator cuff repair, in accordance with the instant disclosure.

FIG. 7 illustrates ultimate failures stress data (MPa) in 6-week and12-week samples for each of three experimental groups in an ovine modelof rotator cuff repair, in accordance with the instant disclosure. Adenotes p<0.001.

FIG. 8 illustrates construct elastic modulus data (MPa) in 6-week and12-week samples for each of three experimental groups in an ovine modelof rotator cuff repair, in accordance with the instant disclosure.

DETAILED DESCRIPTION

This disclosure is not limited to the particular systems, devices andmethods described, as these may vary. The terminology used in thedescription is for the purpose of describing the particular versions orembodiments only, and is not intended to limit the scope of thedisclosure.

The following terms shall have, for the purposes of this application,the respective meanings set forth below. Unless otherwise defined, alltechnical and scientific terms used herein have the same meanings ascommonly understood by one of ordinary skill in the art. Nothing in thisdisclosure is to be construed as an admission that the embodimentsdescribed in this disclosure are not entitled to antedate suchdisclosure by virtue of prior invention.

As used herein, the singular forms “a,” “an,” and “the” include pluralreferences, unless the context clearly dictates otherwise. Thus, forexample, reference to a “fiber” is a reference to one or more fibers andequivalents thereof known to those skilled in the art, and so forth.

As used herein, the term “about” means plus or minus 10% of thenumerical value of the number with which it is being used. Therefore,about 50 mm means in the range of 45 mm to 55 mm.

As used herein, the term “consists of” or “consisting of” means that thedevice or method includes only the elements, steps, or ingredientsspecifically recited in the particular claimed embodiment or claim.

In embodiments or claims where the term comprising is used as thetransition phrase, such embodiments can also be envisioned withreplacement of the term “comprising” with the terms “consisting of” or“consisting essentially of.”

The terms “animal,” “patient,” and “subject” as used herein include, butare not limited to, humans and non-human vertebrates such as wild,domestic, and farm animals. In some embodiments, the terms “animal,”“patient,” and “subject” may refer to humans.

As used herein, the term “long axis,” when referring to a tendon orligament, describes the direction of the tendon or ligament sheath or,if the tendon or ligament does not comprise a sheath, then the axisformed by the connection between the bone and the tendon or ligament.The long axis of a tendon or ligament may also comprise the direction ofthe primary tensile structures, or the stress-bearing axis, of thetendon or ligament.

As used herein, the term “biocompatible” refers to non-harmfulcompatibility with living tissue. Biocompatibility is a broad term thatdescribes a number of materials, including bioinert materials, bioactivematerials, bioabsorbable materials, biostable materials, biotolerantmaterials, or any combination thereof.

The instant disclosure is directed to methods of improving bone-softtissue healing using biocompatible electrospun polymer fibers. In oneembodiment, a method may include locating a portion of a subject's bone,affixing a tendon or ligament to the bone using a hardware fixture, andplacing a patch in physical communication with both the bone and thetendon or ligament, the patch comprising at least one electro spunpolymer fiber. In some embodiments, the bone may be a humerus, and thetendon or ligament may be a supraspinatus tendon. In certainembodiments, the patch may comprise substantially parallel electrospunpolymer fibers, and may be placed such that the fibers are alsosubstantially parallel with the long axis of the tendon or ligament. Inother embodiments, the fibers may be randomly oriented with respect toone another.

Electrospinning Fibers

Electrospinning is a method which may be used to process a polymersolution into a fiber. In embodiments wherein the diameter of theresulting fiber is on the nanometer scale, the fiber may be referred toas a nanofiber. Fibers may be formed into a variety of shapes by using arange of receiving surfaces, such as mandrels or collectors. In someembodiments, a flat shape, such as a sheet or sheet-like fiber mold, afiber scaffold and/or tube, or a tubular lattice, may be formed by usinga substantially round or cylindrical mandrel. In certain embodiments,the electrospun fibers may be cut and/or unrolled from the mandrel as afiber mold to form the sheet. The resulting fiber molds or shapes may beused in many applications, including the repair or replacement ofbiological structures. In some embodiments, the resulting fiber scaffoldmay be implanted into a biological organism or a portion thereof.

Electrospinning methods may involve spinning a fiber from a polymersolution by applying a high DC voltage potential between a polymerinjection system and a mandrel. In some embodiments, one or more chargesmay be applied to one or more components of an electrospinning system.In some embodiments, a charge may be applied to the mandrel, the polymerinjection system, or combinations or portions thereof. Without wishingto be bound by theory, as the polymer solution is ejected from thepolymer injection system, it is thought to be destabilized due to itsexposure to a charge. The destabilized solution may then be attracted toa charged mandrel. As the destabilized solution moves from the polymerinjection system to the mandrel, its solvents may evaporate and thepolymer may stretch, leaving a long, thin fiber that is deposited ontothe mandrel. The polymer solution may form a Taylor cone as it isejected from the polymer injection system and exposed to a charge.

In certain embodiments, a first polymer solution comprising a firstpolymer and a second polymer solution comprising a second polymer mayeach be used in a separate polymer injection system at substantially thesame time to produce one or more electrospun fibers comprising the firstpolymer interspersed with one or more electrospun fibers comprising thesecond polymer. Such a process may be referred to as “co-spinning” or“co-electrospinning,” and a scaffold produced by such a process may bedescribed as a co-spun or co-electrospun scaffold.

Polymer Injection System

A polymer injection system may include any system configured to ejectsome amount of a polymer solution into an atmosphere to permit the flowof the polymer solution from the injection system to the mandrel. Insome embodiments, the polymer injection system may deliver a continuousor linear stream with a controlled volumetric flow rate of a polymersolution to be formed into a fiber. In some embodiments, the polymerinjection system may deliver a variable stream of a polymer solution tobe formed into a fiber. In some embodiments, the polymer injectionsystem may be configured to deliver intermittent streams of a polymersolution to be formed into multiple fibers. In some embodiments, thepolymer injection system may include a syringe under manual or automatedcontrol. In some embodiments, the polymer injection system may includemultiple syringes and multiple needles or needle-like components underindividual or combined manual or automated control. In some embodiments,a multi-syringe polymer injection system may include multiple syringesand multiple needles or needle-like components, with each syringecontaining the same polymer solution. In some embodiments, amulti-syringe polymer injection system may include multiple syringes andmultiple needles or needle-like components, with each syringe containinga different polymer solution. In some embodiments, a charge may beapplied to the polymer injection system, or to a portion thereof. Insome embodiments, a charge may be applied to a needle or needle-likecomponent of the polymer injection system.

In some embodiments, the polymer solution may be ejected from thepolymer injection system at a flow rate of less than or equal to about 5mL/h per needle. In other embodiments, the polymer solution may beejected from the polymer injection system at a flow rate per needle in arange from about 0.01 mL/h to about 50 mL/h. The flow rate at which thepolymer solution is ejected from the polymer injection system per needlemay be, in some non-limiting examples, about 0.01 mL/h, about 0.05 mL/h,about 0.1 mL/h, about 0.5 mL/h, about 1 mL/h, about 2 mL/h, about 3mL/h, about 4 mL/h, about 5 mL/h, about 6 mL/h, about 7 mL/h, about 8mL/h, about 9 mL/h, about 10 mL/h, about 11 mL/h, about 12 mL/h, about13 mL/h, about 14 mL/h, about 15 mL/h, about 16 mL/h, about 17 mL/h,about 18 mL/h, about 19 mL/h, about 20 mL/h, about 21 mL/h, about 22mL/h, about 23 mL/h, about 24 mL/h, about 25 mL/h, about 26 mL/h, about27 mL/h, about 28 mL/h, about 29 mL/h, about 30 mL/h, about 31 mL/h,about 32 mL/h, about 33 mL/h, about 34 mL/h, about 35 mL/h, about 36mL/h, about 37 mL/h, about 38 mL/h, about 39 mL/h, about 40 mL/h, about41 mL/h, about 42 mL/h, about 43 mL/h, about 44 mL/h, about 45 mL/h,about 46 mL/h, about 47 mL/h, about 48 mL/h, about 49 mL/h, about 50mL/h, or any range between any two of these values, including endpoints.

As the polymer solution travels from the polymer injection system towardthe mandrel, the diameter of the resulting fibers may be in the range ofabout 0.1 μm to about 10 μm. Some non-limiting examples of electrospunfiber diameters may include about 0.1 μm, about 0.2 μm, about 0.25 μm,about 0.5 μm, about 1 μm, about 2 μm, about 5 μm, about 10 μm, about 20μm, or ranges between any two of these values, including endpoints. Insome embodiments, the electrospun fiber diameter may be from about 0.25μm to about 20 μm.

Polymer Solution

In some embodiments, the polymer injection system may be filled with apolymer solution. In some embodiments, the polymer solution may compriseone or more polymers. In some embodiments, the polymer solution may be afluid formed into a polymer liquid by the application of heat. A polymersolution may include, for example, non-resorbable polymers, resorbablepolymers, natural polymers, or a combination thereof.

In some embodiments, the polymers may include, for example, polyethyleneterephthalate, polyurethane, polyethylene, polyethylene oxide,polyester, polymethylmethacrylate, polyacrylonitrile, silicone,polycarbonate, polyether ketone ketone, polyether ether ketone,polyether imide, polyamide, polystyrene, polyether sulfone, polysulfone,polyvinyl acetate, polytetrafluoroethylene, polyvinylidene fluoride,polycaprolactone, polylactic acid, polyglycolic acid,polylactide-co-glycolide, polylactide-co-caprolactone, polyglycerolsebacate, polydioxanone, polyhydroxybutyrate, poly-4-hydroxybutyrate),trimethylene carbonate, polydiols, polyesters, collagen, gelatin,fibrin, fibronectin, albumin, hyaluronic acid, elastin, chitosan,alginate, silk, copolymers thereof, and combinations thereof.

It may be understood that polymer solutions may also include acombination of one or more of non-resorbable, resorbable polymers, andnaturally occurring polymers in any combination or compositional ratio.In an alternative embodiment, the polymer solutions may include acombination of two or more non-resorbable polymers, two or moreresorbable polymers or two or more naturally occurring polymers. In somenon-limiting examples, the polymer solution may comprise a weightpercent ratio of, for example, from about 5% to about 90%. Non-limitingexamples of such weight percent ratios may include about 5%, about 10%,about 15%, about 20%, about 25%, about 30%, about 33%, about 35%, about40%, about 45%, about 50%, about 55%, about 60%, about 66%, about 70%,about 75%, about 80%, about 85%, about 90%, or ranges between any two ofthese values, including endpoints.

In some embodiments, the polymer solution may comprise one or moresolvents. In some embodiments, the solvent may comprise, for example,acetone, dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone,N,N-dimethylformamide, Nacetonitrile, hexanes, ether, dioxane, ethylacetate, pyridine, toluene, xylene, tetrahydrofuran, trifluoroaceticacid, hexafluoroisopropanol, acetic acid, dimethylacetamide, chloroform,dichloromethane, water, alcohols, ionic compounds, or combinationsthereof. The concentration range of polymer or polymers in solvent orsolvents may be, without limitation, from about 1 wt % to about 50 wt %.Some non-limiting examples of polymer concentration in solution mayinclude about 1 wt %, 3 wt %, 5 wt %, about 10 wt %, about 15 wt %,about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, about 40 wt%, about 45 wt %, about 50 wt %, or ranges between any two of thesevalues, including endpoints.

In some embodiments, the polymer solution may also include additionalmaterials. Non-limiting examples of such additional materials mayinclude radiation opaque materials, contrast agents, electricallyconductive materials, fluorescent materials, luminescent materials,antibiotics, growth factors, vitamins, cytokines, steroids,anti-inflammatory drugs, small molecules, sugars, salts, peptides,proteins, cell factors, DNA, RNA, other materials to aid in non-invasiveimaging, or any combination thereof. In some embodiments, the radiationopaque materials may include, for example, barium, tantalum, tungsten,iodine, gadolinium, gold, platinum, bismuth, or bismuth (III) oxide. Insome embodiments, the electrically conductive materials may include, forexample, gold, silver, iron, or polyaniline.

In some embodiments, the additional materials may be present in thepolymer solution in an amount from about 1 wt % to about 1500 wt % ofthe polymer mass. In some non-limiting examples, the additionalmaterials may be present in the polymer solution in an amount of about 1wt %, about 5 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about25 wt %, about 30 wt %, about 35 wt %, about 40 wt %, about 45 wt %,about 50 wt %, about 55 wt %, about 60 wt %, about 65 wt %, about 70 wt%, about 75 wt %, about 80 wt %, about 85 wt %, about 90 wt %, about 95wt %, about 100 wt %, about 125 wt %, about 150 wt %, about 175 wt %,about 200 wt %, about 225 wt %, about 250 wt %, about 275 wt %, about300 wt %, about 325 wt %, about 350 wt %, about 375 wt %, about 400 wt%, about 425 wt %, about 450 wt %, about 475 wt %, about 500 wt %, about525 wt %, about 550 wt %, about 575 wt %, about 600 wt %, about 625 wt%, about 650 wt %, about 675 wt %, about 700 wt %, about 725 wt %, about750 wt %, about 775 wt %, about 800 wt %, about 825 wt %, about 850 wt%, about 875 wt %, about 900 wt %, about 925 wt %, about 950 wt %, about975 wt %, about 1000 wt %, about 1025 wt %, about 1050 wt %, about 1075wt %, about 1100 wt %, about 1125 wt %, about 1150 wt %, about 1175 wt%, about 1200 wt %, about 1225 wt %, about 1250 wt %, about 1275 wt %,about 1300 wt %, about 1325 wt %, about 1350 wt %, about 1375 wt %,about 1400 wt %, about 1425 wt %, about 1450 wt %, about 1475 wt %,about 1500 wt %, or any range between any of these two values, includingendpoints. In one embodiment, the polymer solution may include tantalumpresent in an amount of about 10 wt % to about 1,500 wt %.

The type of polymer in the polymer solution may determine thecharacteristics of the electrospun fiber. Some fibers may be composed ofpolymers that are bio-stable and not absorbable or biodegradable whenimplanted. Such fibers may remain generally chemically unchanged for thelength of time in which they remain implanted. Alternatively, fibers maybe composed of polymers that may be absorbed or bio-degraded over time.Such fibers may act as an initial template or scaffold during a healingprocess. These templates or scaffolds may degrade in vivo once thetissues have a degree of healing by natural structures and cells. It maybe further understood that a polymer solution and its resultingelectrospun fiber(s) may be composed or more than one type of polymer,and that each polymer therein may have a specific characteristic, suchas bio-stability or biodegradability.

Applying Charges to Electrospinning Components

In an electrospinning system, one or more charges may be applied to oneor more components, or portions of components, such as, for example, amandrel or a polymer injection system, or portions thereof. In someembodiments, a positive charge may be applied to the polymer injectionsystem, or portions thereof. In some embodiments, a negative charge maybe applied to the polymer injection system, or portions thereof. In someembodiments, the polymer injection system, or portions thereof, may begrounded. In some embodiments, a positive charge may be applied tomandrel, or portions thereof. In some embodiments, a negative charge maybe applied to the mandrel, or portions thereof. In some embodiments, themandrel, or portions thereof, may be grounded. In some embodiments, oneor more components or portions thereof may receive the same charge. Insome embodiments, one or more components, or portions thereof, mayreceive one or more different charges.

The charge applied to any component of the electrospinning system, orportions thereof, may be from about −15 kV to about 30 kV, includingendpoints. In some non-limiting examples, the charge applied to anycomponent of the electrospinning system, or portions thereof, may beabout −15 kV, about −10 kV, about −5 kV, about −4 kV, about −3 kV, about−1 kV, about −0.01 kV, about 0.01 kV, about 1 kV, about 5 kV, about 10kV, about 11 kV, about 11.1 kV, about 12 kV, about 15 kV, about 20 kV,about 25 kV, about 30 kV, or any range between any two of these values,including endpoints. In some embodiments, any component of theelectrospinning system, or portions thereof, may be grounded.

Mandrel Movement During Electrospinning

During electrospinning, in some embodiments, the mandrel may move withrespect to the polymer injection system. In some embodiments, thepolymer injection system may move with respect to the mandrel. Themovement of one electrospinning component with respect to anotherelectrospinning component may be, for example, substantially rotational,substantially translational, or any combination thereof. In someembodiments, one or more components of the electrospinning system maymove under manual control. In some embodiments, one or more componentsof the electrospinning system may move under automated control. In someembodiments, the mandrel may be in contact with or mounted upon asupport structure that may be moved using one or more motors or motioncontrol systems. The pattern of the electrospun fiber deposited on themandrel may depend upon the one or more motions of the mandrel withrespect to the polymer injection system. In some embodiments, themandrel surface may be configured to rotate about its long axis. In onenon-limiting example, a mandrel having a rotation rate about its longaxis that is faster than a translation rate along a linear axis, mayresult in a nearly helical deposition of an electrospun fiber, formingwindings about the mandrel. In another example, a mandrel having atranslation rate along a linear axis that is faster than a rotation rateabout a rotational axis, may result in a roughly linear deposition of anelectrospun fiber along a liner extent of the mandrel.

Methods of Improving Bone-Soft Tissue Healing

The instant disclosure is directed to methods of improving bone-softtissue healing using biocompatible electrospun polymer fibers. It may beunderstood that the methods described herein may be applied to anybone-soft tissue interface, and that the tendon-bone and ligament-boneinterface examples described herein are non-limiting.

Without wishing to be bound by theory, during surgery, the debridementof at least a portion of a subject's bone near the area where the softtissue is meant to be reattached may induce bleeding, thereby increasingthe number of healing and growth factors in the localized area. Such anincrease may promote healing at the bone-soft tissue interface. In someembodiments, the use of a patch comprising one or more electrospunpolymer fibers may further improve healing at the interface, perhaps byproviding a matrix for the cells to attach, or perhaps by facilitatingthe migration of cells from healthy tissues to the repair site. Incertain embodiments, aligning the electrospun polymer fibers with thelong axis of the soft tissue to be repaired may further facilitate suchmigration. In other embodiments, randomly aligned electrospun polymerfibers may be sufficient to facilitate cell migration and interfacehealing. Debridement is an optional step of the methods describedherein.

In some embodiments, the methods described herein may also contribute tothe healing and/or reformation of Sharpey's fibers, which are fibrousportions of bone tissue that may serve to anchor soft tissue to boneduring healing at a bone-soft tissue interface. Without wishing to bebound by theory, the electrospun polymer fiber constructs describedherein may serve to improve the speed and/or strength of the formationand/or reestablishment of Sharpey's fibers at the bone-soft tissueinterface. In some embodiments, a patch comprising substantiallyparallel electrospun polymer fibers may help form or restore Sharpey'sfibers, and/or may increase the rate at which such fibers are formed orrestored at a bone-soft tissue interface. In other embodiments, a patchcomprising randomly oriented electrospun polymer fibers may help form orrestore Sharpey's fibers, and/or may increase the rate at which suchfibers are formed or restored at a bone-soft tissue interface. In someembodiments, a patch comprising a combination of randomly oriented andsubstantially parallel electrospun polymer fibers may help restoreSharpey's fibers, and/or may increase the rate at which such fibers areformed or restored at a bone-soft tissue interface. In some embodiments,any of the patches described herein may help form or restore Sharpey'sfibers at the bone-soft tissue interface that may comprise substantiallythe same density as those found in original, uninjured bone-soft tissueinterfaces.

In one embodiment, a method may comprise locating at least a portion ofa subject's bone, affixing a tendon or ligament to the bone using ahardware fixture, and placing a patch in physical communication withboth the bone and the tendon or ligament, the patch comprising at leastone electrospun polymer fiber. In some embodiments, the method mayconsist only of these steps. In certain embodiments, locating at least aportion of a subject's bone may further comprise debriding at least aportion of the subject's bone.

In some embodiments, the hardware fixture may comprise a suture inphysical communication with a suture anchor. In other embodiments, thehardware fixture may comprise a screw, an interference screw, an anchorthat does not include a suture, or any equivalent hardware fixturesknown for use in orthopedics.

In some embodiments, the patch may be in physical communication with theportion of the subject's bone that has been debrided. In certainembodiments, the patch may comprise substantially parallel electrospunpolymer fibers, and may be placed such that the fibers are alsosubstantially parallel with the long axis of the tendon or ligament. Inother embodiments, the patch pay comprise randomly oriented electrospunpolymer fibers. In still other embodiments, the patch may comprise acombination of randomly oriented and substantially parallel electrospunpolymer fibers. In some embodiments, the patch may be positioned at ahealing interface between the bone and the tendon or ligament.

In some embodiments, the suture may comprise one or more sutures. Insome embodiments, the one or more sutures may extend through the patch.FIG. 1 and FIG. 2 illustrate embodiments of a suture in communicationwith a suture anchor (not shown) extending through a patch. In anotherembodiment, the one or more sutures may extend through an opening in thepatch. In some embodiments, the patch may surround or substantiallysurround the area from which the one or more sutures extends. In anotherembodiment, the one or more sutures may extend from approximately thecenter of the patch.

In some embodiments, the bone may be, for example, a humerus, a radius,an ulna, a tibia, a femur, a calcaneus, or any combination thereof. Inone embodiment, the bone is a humerus. In another embodiment, the boneis selected from a femur and a tibia.

In some embodiments, the tendon or ligament may be, for example, asupraspinatus tendon, an infraspinatus tendon, a subscapularis tendon, adeltoid tendon, a biceps tendon, a triceps tendon, an anterior cruciateligament, a posterior cruciate ligament, a medial collateral ligament, alateral collateral ligament, an illiotibial band, a quadriceps tendon, ahamstring tendon, a sartorius tendon, an Achilles tendon, a tibialisanterior tendon, or any combination thereof. In one embodiment, thetendon or ligament is a supraspinatus tendon. In another embodiment, thetendon or ligament is an anterior cruciate ligament.

In some embodiments, the patch may comprise one or more electrospunpolymer fibers. In certain embodiments, the electrospun polymer fibersmay have a diameter in the range of about 0.1 μm to about 10 μm. Somenon-limiting examples of electrospun fiber diameters may include about0.1 μm, about 0.2 μm, about 0.25 μm, about 0.5 μm, about 1 μm, about 2μm, about 3 μm, about 4 μm, about 5 μm, about 6 μm, about 7 μm, about 8μm, about 9 μm, about 10 μm, about 11 μm, about 12 μm, about 13 μm,about 14 μm, about 15 μm, about 16 μm, about 17 μm, about 18 μm, about19 μm, about 20 μm, or ranges between any two of these values, includingendpoints. In some embodiments, the electrospun fiber diameter may befrom about 0.25 μm to about 20 μm.

In some embodiments, the patch may have, independently, a length fromabout 1 mm to about 100 mm, and a width from about 1 mm to about 100 mm.The patch may have, independently, a length or width of about, forexample, about 1 mm, about 5 mm, about 10 mm, about 15 mm, about 20 mm,about 25 mm, about 30 mm, about 35 mm, about 40 mm, about 45 mm, about50 mm, about 55 mm, about 60 mm, about 65 mm, about 70 mm, about 75 mm,about 80 mm, about 85 mm, about 90 mm, about 95 mm, about 100 mm, or anyrange between any two of these values, including endpoints.

In some embodiments, the patch may have a thickness from about 100 μm toabout 5,000 μm. The patch may have a thickness of, for example, about100 μm, about 200 μm, about 300 μm, about 400 μm, about 500 μm, about600 μm, about 700 μm, about 800 μm, about 900 μm, about 1,000 μm, about1,250 μm, about 1,500 μm, about 1,750 μm, about 2,000 μm, about 2,250μm, about 2,500 μm, about 2,750 μm, about 3,000 μm, about 3,250 μm,about 3,500 μm, about 3,750 μm, about 4,000 μm, about 4,250 μm, about4,500 μm, about 4,750 μm, about 5,000 μm, or any range between any twoof these values, including endpoints.

In some embodiments, the patch may comprise one or more pores. Incertain embodiments, the pores are uniformly, or substantiallyuniformly, distributed throughout the patch, while in other embodimentsthe pores are irregularly distributed within the patch. In someembodiments, the pores may have a diameter from about 0.25 μm to about50 μm. The diameter of the pores may be, for example, about 0.25 μm,about 0.5 μm, about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5μm, about 10 μm, about 15 μm, about 20 μm, about 25 μm, about 30 μm,about 35 μm, about 40 μm, about 45 μm, about 50 μm, or any range betweenany two of these values, including endpoints.

In some embodiments, the patch may have particular mechanicalproperties, such as a particular Young's modulus, suture retentionstrength, radial stiffness, or bursting strength. In some embodiments,the Young's modulus of the patch may be from about 0.5 MPa to about1,000 MPa. The Young's modulus may be, for example, about 0.5MPA, about1 MPa, about 10 MPa, about 20 MPa, about 30 MPa, about 40 MPa, about 50MPa, about 60 MPa, about 70 MPa, about 80 MPa, about 90 MPa, about 100MPa, about 110 MPa, about 120 MPa, about 130 MPa, about 140 MPa, about150 MPa, about 160 MPa, about 170 MPa, about 180 MPa, about 190 MPa,about 200 MPa, about 210 MPa, about 220 MPa, about 230 MPa, about 240MPa, about 250 MPa, about 260 MPa, about 270 MPa, about 280 MPa, about290 MPa, about 300 MPa, about 310 MPa, about 320 MPa, about 330 MPa,about 340 MPa, about 350 MPa, about 360 MPa, about 370 MPa, about 380MPa, about 390 MPa, about 400 MPa, about 410 MPa, about 420 MPa, about430 MPa, about 440 MPa, about 450 MPa, about 460 MPa, about 470 MPa,about 480 MPa, about 490 MPa, about 500 MPa, about 510 MPa, about 520MPa, about 530 MPa, about 540 MPa, about 550 MPa, about 560 MPa, about570 MPa, about 580 MPa, about 590 MPa, about 600 MPa, about 610 MPa,about 620 MPa, about 630 MPa, about 640 MPa, about 650 MPa, about 660MPa, about 670 MPa, about 680 MPa, about 690 MPa, about 700 MPa, about710 MPa, about 720 MPa, about 730 MPa, about 740 MPa, about 750 MPa,about 760 MPa, about 770 MPa, about 780 MPa, about 790 MPa, about 800MPa, about 810 MPa, about 820 MPa, about 830 MPa, about 840 MPa, about850 MPa, about 860 MPa, about 870 MPa, about 880 MPa, about 890 MPa,about 900 MPa, about 910 MPa, about 920 MPa, about 930 MPa, about 940MPa, about 950 MPa, about 960 MPa, about 970 MPa, about 980 MPa, about990 MPa, about 1,000 MPa, or any range between any two of these values,including endpoints.

In some embodiments, the patch may comprise at least one layer ofelectrospun polymer fibers that are substantially parallel with respectto one another. In some embodiments, the patch may comprise more thanone layer, and the electrospun polymer fibers of a first layer may besubstantially parallel with respect to one another and substantiallyparallel to the fibers of any additional layers. In other embodiments,the patch may comprise more than one layer, and the electrospun polymerfibers of a first layer may be substantially parallel with respect toone another and substantially perpendicular to the fibers of anyadditional layers. A layer may include a sheet, such that a first layermay comprise a first sheet, and a second layer may comprise a secondsheet, and so on, similar to how textiles may include more than onelayer of material.

In some embodiments, the patch may be placed such that the substantiallyparallel electrospun polymer fibers are substantially parallel with thelong axis of the tendon or ligament to be repaired. In some embodiments,the substantially parallel electrospun polymer fibers and, optionally,their alignment with the long axis of the tendon or ligament to berepaired, may be configured to facilitate the migration of cells to thesite of the repair.

In some embodiments, the patch may further comprise additionalmaterials. The additional materials may be, for example, tricalciumphosphate, hydroxyapatite, bioglass, or any combination thereof.

In additional embodiments, the patch may further comprise a biologiccomponent. The biologic component may be, for example, mesenchymal stemcells, tenocytes, fibroblasts, osteoblasts, platelet-rich plasma, bonemarrow aspirate, stromal vascular fraction, bursa cells, amnion, growthfactors, or any combination thereof.

In some embodiments, the at least one electrospun polymer fiber maycomprise a polymer selected from the group consisting of polyethyleneterephthalate, polyurethane, polyethylene, polyethylene oxide,polyester, polymethylmethacrylate, polyacrylonitrile, silicone,polycarbonate, polyether ketone ketone, polyether ether ketone,polyether imide, polyamide, polystyrene, polyether sulfone, polysulfone,polyvinyl acetate, polytetrafluoroethylene, polyvinylidene fluoride,polycaprolactone, polylactic acid, polyglycolic acid,polylactide-co-glycolide, polylactide-co-caprolactone, polyglycerol sebac ate, polydioxanone, polyhydroxybutyrate, poly-4-hydroxybutyrate),trimethylene carbonate, polydiols, polyesters, collagen, gelatin,fibrin, fibronectin, albumin, hyaluronic acid, elastin, chitosan,alginate, silk, copolymers thereof, or any combination thereof. In someembodiments, the at least one electrospun polymer fiber may comprise aco-spun combination of about 20 wt % of fibers comprising polyethyleneterephthalate and about 80 wt % of fibers comprising polyurethane. Inother embodiments, the at least one electrospun polymer fiber maycomprise a co-spun combination of about 50 wt % of fibers comprisingpolylactide-co-caprolactone fibers and about 50 wt % of fiberscomprising polyglycolic acid. In still other embodiments, the at leastone electrospun polymer fiber may comprise at least a first fibercomprising polylactide-co-caprolactone and at least a second fibercomprising polyglycolic acid, wherein the first fiber and the secondfiber are co-spun (sometimes referred to as “co-electrospun”).

In another embodiment, a method may comprise locating a humerus of asubject, affixing a supraspinatus tendon to the humerus using a sutureanchor in physical communication with a suture, and placing a patchcomprising at least one electrospun polymer fiber in physicalcommunication with the humerus and the supraspinatus tendon, such thatthe patch is between the humerus and the supraspinatus tendon, and thesuture extends through an opening in the patch. In one embodiment, themethod consists of only these steps. In other embodiments, the step oflocating a humerus of a subject may further comprise debriding at leasta portion of the humerus of the subject.

EXAMPLES Example 1 Ovine Rotator Cuff Repair Model

The objective of this study was to examine the bone ingrowth, localtissue response, and biomechanical effectiveness of repair of therotator cuff with embodiments of the scaffolds and methods describedherein in an ovine (sheep) model. Forty animals were divided into twogroups: a treatment group (20 animals), which was treated with ascaffold as described herein, and a control group (20 animals), whichunderwent rotator cuff repairs, but did not receive a scaffold. Thecontralateral untreated shoulders of 10 animals were collected and usedas untreated samples.

In the treatment and control groups, the right infraspinatus tendon wascompletely transected at the humeral attachment and acutely reattachedto the humeral footprint using a total of four suture anchors. In thetreatment group, a scaffold was sandwiched between the infraspinatustendon and humeral footprint. Ten animals from each group weresacrificed 6 weeks after the repair, and the remaining ten animals fromeach group were sacrificed 12 weeks after the repair.

Of the 10 animals in each group sacrificed at 6 weeks, 5 animals in eachgroup were processed for biomechanical testing of the strength of therepair, and the other 5 animals in each group were processed forhistology of the bone-tendon interface. Of the 10 animals in each groupsacrificed at 12 weeks, 5 animals in each group were processed forbiomechanical testing of the strength of the repair, and 5 animals wereprocessed for histology of the bone-tendon interface as well as overallorgan pathology assessment. In addition, the contralateral untreatedshoulders of 10 animals were collected and used as untreated samples. Ofthose ten contralateral untreated shoulders, 5 were processed forbiomechanical testing of the strength of the unrepaired rotator cuff,and the other 5 were processed for histology of the bone-tendoninterface.

Gross dissection was completed at necropsy for each animal. Freshhumerus-infraspinatus tendon constructs were delivered to abioengineering research laboratory within hours of animal sacrifice,accompanied by a necropsy record. The extraneous soft tissue was removedfrom each shoulder. Samples were digitally imaged and radiographed.Samples slated for histological analysis were placed in 10% neutralbuffered formalin.

Samples slated for biomechanical analysis underwent testing in twophases: (A) preconditioning, and (B) ramp to failure. Ramp to failurewas performed last because it is a destructive test. All loads impartedon the samples were applied quasi-statically and aligned collinear tothe physiologic loading direction of the tendon. Each ovineinfraspinatus tendon—humerus bone construct was mounted in a mechanicaltesting (MTS) system prior to biomechanical assessment. High-contrastreflective markers were attached to the tendon, segmenting three regionsof interest (ROIs) within the tendon: proximal, middle, and distal tothe surgical repair site. Digital image correlation was used to track 2Dcontrast marker displacement during loading.

(A) Preconditioning: To minimize the viscoelastic effects on themeasured biomechanical response, ten cyclic tensile loads rangingbetween 0 and 2% strain were applied to precondition the tendon. Thepreconditioning phase was preceded by a ˜2 minute preload phase. Astatic preload of 10 N was applied to all specimens for ˜2 minutes oruntil the specimen was fully relaxed. The sample's reference gaugelength was measured as the tendon's distance, in millimeters, from thebottom of the cryo-clamp's grip to the tendon's insertion into thehumerus following the 10 N preload.

(B) Ramp to failure: To characterize structural and material propertiesof the repaired tissue, the specimens were quasi-statically loaded tofailure at a rate of 0.5% strain/sec. Load and displacement data wereacquired at 25 Hz (due to slow loading rate and to allow registrationwith the DIC data). Digital videos were collected at 25 Hz during rampto failure testing for DIC analysis. Digital photographs were taken ofeach specimen after failure to document the location and mode of failure(MOF). Photographs identified the Animal ID Number and StudyIdentification Number (at a minimum).

Structural properties representing the biomechanical behavior of thebone-tendon construct and material properties representing thebiomechanical behavior at the tissue level were calculated. Force (N)and displacement (mm) data were used to characterize structuralproperties, including ultimate load (N) and stiffness (N/mm). Materialproperties were calculated from structural measurements by normalizationto cross-sectional area or to the initial gauge length of the sample.Material property calculations included ultimate stress (MPa), ultimatestrain (mm/mm), and elastic modulus (MPa). 2D displacements of thereflective markers adhered to the tendon were tracked throughout ramp tofailure testing to determine the localized strain in the tendon atultimate load, using digital image correlation. Localized strain (mm/mm)at the ultimate load was calculated for three discrete regions ofinterest (ROI): (i) proximal ROI (i.e. the region spanning the originalsurgery site); (ii) middle ROI (i.e. the region adjacent to the originalsurgery site); and (iii) distal ROI (i.e. the region encompassing themid-substance of the tendon). Mode of failure (MOF) was also calculated.Possible modes of failure included (a) failure at the repair site; (b)mid-substance failure, (c) bone avulsion; and (d) failure at the repairsite and mid-substance failure (i.e. a mixed failure mode).

As described above, ten (treatment group n=5; control group n=5) animalswere allocated for histological analysis per sacrifice time point.Organs of interest were also collected from the animals sacrificed at 12weeks, and were placed in 10% neutral buffered formalin for fixationprior to histology processing.

Following gross dissection and fixation (including a minimum of twoweeks in formalin), samples were bisected through the infraspinatus andhumeral attachment sites, creating a slab of tissue in the sagittalplane containing the humerus+bone anchor(s), repair site (i.e., thefootprint) and surrounding tendon soft tissue(s). Images of the grosstissue blocks were taken. After fixation, the tissue was dehydrated ingraded solutions of ETOH on a tissue processor. After processing, thesamples were cleared with acetone and polymerized into a hardenedplastic block using Hard Acrylosin.

Histological sections were taken in the sagittal plane to display thehumerus+bone anchor(s), repair site (i.e., the footprint) andsurrounding soft tissue. Three slide sections were cut through each ROI.Initial sections were taken using a diamond blade bone saw at athickness of approximately 300-400 μm. All sections were ground using amicrogrinder to 60-70 μm thickness and stained. Sections were firststained with Sanderson's Rapid bone stain, which providesdifferentiation of cells within the section and allows detection ofcartilage within the tissue. Slides were then counterstained using a VanGieson bone stain that allows differentiation of collagen and detectionof bone (immature woven bone and mature lamellar bone) within thesection.

2 time points×2 treatment groups (treatment and control)×5 samples pergroup×2 slides per group yielded a total of 40 slides from thesurgically treated samples (i.e. 20 slides from the treatment group and20 slides from the control group). Five contralateral shoulders(untreated controls) were also allocated for slide production, andyielded 2 slides per ROI for a total of 10 untreated slides.

High-resolution digital images were acquired by field for the allsurgical site slides using a Nikon E800 microscope, a Spot digitalcamera, and a Pentium IBM-based computer with expanded memorycapabilities. Organ slides were not imaged.

Image Pro software was used for histomorphometric measurements on theanchor-bone ROIs. Histomorphometric measurements were performed oncalibrated digital images to quantify: (i) percent bone area within theROI; (ii) percent fibrous tissue within the ROI; and (iii) percentimplant area within the ROI.

Slides were delivered to a certified pathologist for histopathologyanalysis. The outcome data included a quantitative scoring of thefollowing parameters: (i) cellular analysis; (ii) inflammatory/foreignanalysis; (iii) fiber alignment; (iv) implant degradation; (v)osteoblast/osteoclast activity; (vi) osteogenic response; and (vii)comparison to untreated samples (shoulder surgical site slides only).

FIG. 3A illustrates a histological sample of an untreated controlrotator cuff (i.e. a contralateral control). FIG. 3B illustrates ahistological sample of a treated control rotator cuff at 6 weeks (i.e. arotator cuff that underwent a repair but did not receive a scaffold asdescribed herein). FIG. 3C illustrates a histological sample of atreated rotator cuff at 6 weeks (i.e. a rotator cuff that underwent arepair and received a scaffold as described herein). This histologyillustrates a fibrous scar between the bone and tendon with the suturerepair in the samples repaired without a scaffold (e.g. FIG. 3B). Such ascar was not present in the samples repaired with a scaffold asdescribed herein (e.g. FIG. 3C).

FIG. 4A illustrates a histological sample of an untreated controlrotator cuff (i.e. a contralateral control). FIG. 4B illustrates ahistological sample of a treated control rotator cuff at 12 weeks (i.e.a rotator cuff that underwent a repair but did not receive a scaffold asdescribed herein). FIG. 4C illustrates a histological sample of atreated rotator cuff at 12 weeks (i.e. a rotator cuff that underwent arepair and received a scaffold as described herein). This histologyillustrates a fibrous scar between the bone and tendon with the suturerepair in the samples repaired without a scaffold (e.g. FIG. 4B). Such ascar was not present in the samples repaired with a scaffold asdescribed herein (e.g. FIG. 4C).

FIG. 4B illustrates that, overall at the sub-gross level, the tendonappears similar in thickness to normal or un-manipulated ovineinfraspinatus tendon. There is a moderate degree of organization ofcollagen bundles of the tendon, with some parallel arrangement, however,the organization of collagen is less than that observed in FIG. 4C, withmore broad collagen bundles arranged in a haphazard and intersectingmanner.

The tendon to bone insertion/enthesis appears more consistent with an“indirect” or Fibrous-type of insertion characterized by diffuse densetendon-like fibrous tissue immediately attaching along the entiresurface of the bone/humeral head. There is no real attempt atre-establishment of a direct/fibrocartilaginous enthesis, with onlysmall focal and extremely thin layers of fibrocartilage (calcified andun-calcified) attaching the tendon to the bone. This cartilage accountsfor <5% of surface area between the tendon and bone. Minimal to noinflammation or fibrovascular/granulation tissue is observed.

In FIG. 4C, overall, at the sub-gross level, the tendon appears similarin thickness and organization to normal or un-manipulated ovineinfraspinatus tendon. Generally, collagen bundles of the tendon arepredominately arranged in more tightly packed parallel bundles.

The insertion of the fibrous tendon with the humeral footprint isbeginning to be organized in a manner similar to the “native”direct/fibrocartilaginous insertion of the ovine infraspinatus tendon.Diffusely spanning the majority of the surface area (˜75%) of thehumeral head/footprint, there is transition from the dense fibrousconnective tissue of the tendon to first, a very thin layer ofuncalcified fibrocartilage, and then to a more broad/thick layer ofcalcified fibrocartilage immediately adjacent to the surface of thebone. This organization of the tendon attachment is reminiscent of thedirect/fibrocartilaginous type of enthesis native to the ovineinfraspinatous tendon with the following exceptions: 1) the attachmentand transition of the tendon to fibrocartilage is more diffuse acrossthe entire bone surface of the humeral head as opposed to a more focalattachment typically observed in normal control animals; 2) while anorganization of the zones of the enthesis (uncalcified and calcifiedfibrocartilage) is present and observed, these zones are more thin andless prominent than those observed in a normal control animal; and 3)the calcified fibrocartilage is more similar to hyaline-like cartilageand not uniformly composed linear stacks of chondrocytes arrangedperpendicular to the bone. Focally, prominent collagen fibers, similarto “Sharpey” fibers, extend through a region of calcified fibrocartilageand attach to remnant scaffold and the humeral head. Minimal to noinflammation or fibrovascular/granulation tissue was observed.

FIG. 5 illustrates ultimate failure load data (N) in the 6-week and12-week samples for each of the three experimental groups (repair withno scaffold; repair with scaffold; and contralateral control).Comparisons of the means within this set of data had statistical valuesas shown in Table 1 (note that contralateral samples were not includedin the 2-way ANOVA analysis). While the difference in mean valuesbetween the experimental groups was not statistically significant, thedifference was clinically significant. The lack of statisticalsignificance is due to the large variance in the no-scaffold group at 12weeks, ranging from 89N to 2,987N within this small population of n=10per group. The difference in mean values between the no-scaffold andscaffold groups at 12 weeks represents an increase in ultimate failureload of 48%, while the difference in median values between these twogroups at 12 weeks represents an increase in ultimate failure load of74% in the scaffold group. The improved reliability and consistency inthe scaffold group, illustrated by the small variance in the scaffoldgroup compared to the no-scaffold group, is a surprising result thatunderscores the clinical utility of the embodiments described herein.

TABLE 1 Comparisons for Factor p-value Across time (A) p = 0.003 Acrosstreatments p = 0.188 Within 6 weeks p = 0.682 Within 12 weeks p = 0.147Time within “No Scaffold” p = 0.066 Time within “Scaffold” (B) p = 0.007

FIG. 6 illustrates construct stiffness data (N/mm) in the 6-week and12-week samples for each of the three experimental groups (repair withno scaffold; repair with scaffold; and contralateral control).Comparisons within this set of data had statistical values as shown inTable 2 (note that contralateral samples were not included in the 2-wayANOVA analysis). There was no statistically significant interactionbetween treatment and time (p=0.361).

TABLE 2 Comparisons for Factor p-value Across time p = 0.158 Acrosstreatments p = 0.406

FIG. 7 illustrates ultimate failure stress data (MPa) in the 6-week and12-week samples for each of the three experimental groups (repair withno scaffold; repair with scaffold; and contralateral control).Comparisons within this set of data had statistical values as shown inTable 3 (note that contralateral samples were not included in the 2-wayANOVA analysis). There was no statistically significant interactionbetween treatment and time (p=0.372).

TABLE 3 Comparisons for Factor p-value Across time (A) p <0.001 Acrosstreatments p = 0.370

FIG. 8 illustrates construct elastic modulus data (MPa) in the 6-weekand 12-week samples for each of the three experimental groups (repairwith no scaffold; repair with scaffold; and contralateral control).Comparisons within this set of data had statistical values as shown inTable 4 (note that contralateral samples were not included in the 2-wayANOVA analysis). There was no statistically significant interactionbetween treatment and time (p=0.889).

TABLE 4 Comparisons for Factor p-value Across time p = 0.175 Acrosstreatments p = 0.907

In summary, the rotator cuffs repaired using a scaffold as describedherein demonstrated a 33% increase in breaking strength over the rotatorcuffs repaired without such a scaffold at 6 weeks, and a 50% increase at12 weeks. Histology showed a fibrous scar between the bone and tendonwith the suture repair in the samples repaired without a scaffold. Sucha scar was not present in the samples repaired with a scaffold asdescribed herein.

While the present disclosure has been illustrated by the description ofexemplary embodiments thereof, and while the embodiments have beendescribed in certain detail, it is not the intention of the Applicantsto restrict or in any way limit the scope of the appended claims to suchdetail. Additional advantages and modifications will readily appear tothose skilled in the art. Therefore, the disclosure in its broaderaspects is not limited to any of the specific details, representativedevices and methods, and/or illustrative examples shown and described.Accordingly, departures may be made from such details without departingfrom the spirit or scope of the Applicant's general inventive concept.

1-44. (canceled)
 45. A patch comprising: at least one electrospunpolymer fiber configured to be placed in physical communication with abone and a tendon or a ligament; wherein the at least one electrospunpolymer fiber comprises at least one layer of electrospun polymer fibersthat are randomly oriented with respect to one another; wherein thepatch is configured to promote healing at an interface between the boneand the tendon or the ligament.
 46. The patch of claim 45, wherein thebone is selected from the group consisting of a humerus, a radius, anulna, a tibia, a femur, a calcaneus, and combinations thereof.
 47. Thepatch of claim 45, wherein the tendon or the ligament is selected fromthe group consisting of a supraspinatus tendon, an infraspinatus tendon,a subscapularis tendon, a deltoid tendon, a biceps tendon, a tricepstendon, an anterior cruciate ligament, a posterior cruciate ligament, amedial collateral ligament, a lateral collateral ligament, anilliotibial band, a quadriceps tendon, a hamstring tendon, a sartoriustendon, an Achilles tendon, a tibialis anterior tendon, and combinationsthereof.
 48. The patch of claim 45, further comprising a hardwarefixture selected from the group consisting of a suture anchor inphysical communication with a suture, an interference screw, an anchor,and combinations thereof.
 49. The patch of claim 48, wherein thehardware fixture comprises a suture anchor in physical communicationwith a suture, and wherein the suture extends through an opening in thepatch.
 50. The patch of claim 45, wherein the at least one electrospunpolymer fiber has a diameter of about 0.25 μm to about 20 μm.
 51. Thepatch of claim 45, having a length of about 1 mm to about 100 mm, awidth of about 1 mm to about 100 mm, and a thickness of about 100 μm toabout 5,000 μm.
 52. The patch of claim 45, further comprising a materialselected from the group consisting of tricalcium phosphate,hydroxyapatite, bioglass, and combinations thereof.
 53. The patch ofclaim 45, further comprising a biologic component selected from thegroup consisting of mesenchymal stem cells, tenocytes, fibroblasts,osteoblasts, platelet-rich plasma, bone marrow aspirate, stromalvascular fraction, bursa cells, amnion, growth factors, and combinationsthereof.
 54. The patch of claim 45, wherein the at least one electrospunpolymer fiber comprises a polymer selected from the group consisting ofpolyethylene terephthalate, polyurethane, polyethylene, polyethyleneoxide, polyester, polymethylmethacrylate, polyacrylonitrile, silicone,polycarbonate, polyether ketone ketone, polyether ether ketone,polyether imide, polyamide, polystyrene, polyether sulfone, polysulfone,polyvinyl acetate, polytetrafluoroethylene, polyvinylidene fluoride,polycaprolactone, polylactic acid, polyglycolic acid,polylactide-co-glycolide, polylactide-co-caprolactone, polyglycerolsebacate, polydioxanone, polyhydroxybutyrate, poly-4-hydroxybutyrate,trimethylene carbonate, polydiols, polyesters, collagen, gelatin,fibrin, fibronectin, albumin, hyaluronic acid, elastin, chitosan,alginate, silk, copolymers thereof, and combinations thereof.
 55. Thepatch of claim 45, wherein the at least one electrospun fiber comprisesa first fiber comprising polylactide-co-caprolactone and a second fibercomprising polyglycolic acid, and wherein the first fiber and the secondfiber are co-spun.
 56. The patch of claim 45, wherein the at least oneelectrospun fiber comprises a co-spun combination of about 50 wt % offibers comprising polylactide-co-caprolactone fibers and about 50 wt %of fibers comprising polyglycolic acid.